Oxidative changes of lens proteins are thought to occur with aging and to contribute to the development of cataracts. The goals of this project are to determine (1) the extent of oxidative modification of crystallins and metabolic enzymes in both normal and cataractous lenses, (2) the nature of the modifications and mechanisms leading to the changes, and (3) the modifications on the structure and function of lens proteins. Bovine and rat lenses are used. The approach is to study the modifications of lens proteins after treatment in vitro by metal-catalyzed oxidation systems. The focus of these studies has been on the modification of bovine gamma-crystallins as a model system. There are distinct differences in the interaction of metals with each of the purified gamma-crystallins. The structural modifications induced by treatment of the crystallins with metal-catalyzed oxidation have been studied. A protein that presumably protects against metal-catalyzed oxidation in cells has been identified in the eye of rats, bovine, primates, and humans; the bovine lens protein has been purified. We have studied human lens proteins by two-dimensional polyacrylamide gel electrophoresis. These studies have included identification of the human lens proteins, protein distribution within the lens, age-related changes in composition, and identification of the age-related modifications that the proteins undergo.